NOF Fluoxastrobin Petition for Tolerance in or on Avocado, Barley, Canola (Rapeseed Subgroup 20A), and Dried Shelled Pea and Bean (Crop Subgroup 6c)

EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: Hope Johnson (PM 21), 703-305-5410

. 

Arysta LifeScience North America, LLC 

[Insert petition number] 

Summary of Petitions 

EPA has received a pesticide petition ([insert petition number]) from Arysta LifeScience 

North America, LLC 15401 Weston Parkway, Suite 150, Cary, North Carolina 27513

proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act 

(FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 by establishing a tolerance for 

residues of Fluoxastrobin, [(1E)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4-

pyrimydinyl]oxy]phenyl] (5,6dihydro-l,4,2-dioxazin-3-yl)methanone O-methyloxime, and

its Z isomer, (1Z)-[2-[[6-(2chlorophenoxy)-5-fluoro-4-pyrimydinyl] oxy]phenyl] (5,6-

dihydro-l,4,2-dioxazin-3yl)methanone O-methyloxime] in or on the raw agricultural 

commodities avocado at 0.9 parts per million (ppm); barley, grain at 0.4 ppm; barley, hay 

at 15 ppm; barley, straw at 15 ppm; Rapeseed subgroup 20A at 0.8 ppm; and Dried shelled 

pea and bean (except soybean) subgroup 6C at 0.2 ppm. EPA has determined that the 

petition contains data or information regarding the elements set forth in section 408 (d)(2) 

of FDDCA; however, EPA has not fully evaluated the sufficiency of the submitted data at 

this time or whether the data supports granting of the petition. Additional data may be 

needed before EPA rules on the petition.

A. Residue Chemistry 

1. Plant metabolism. The metabolism of fluoxastrobin in plants is adequately understood

as published in the Federal Register of April 23, 2003 (68 FR19991). Studies have been 

conducted to delineate the metabolism of radiolabeled fluoxastrobin in peanut, tomato, 

spring wheat, and various representative rotational crops, all showing similar results. The 

residue of concern is parent fluoxastrobin (sum of E and Z isomer). 

2. Analytical method. Adequate analytical methodology is available for enforcement 

purposes. The method comprises microwave solvent extraction followed by a solid phase 

extraction clean up and quantification by high performance liquid chromatography with 

tandem mass spectrometric detection (HPLC/MS/MS). The individual detector responses 

for measured E- and Z-isomers is summed to give total residue. The validated limit of 

quantitation is 0.01 ppm for all matrices.

3. Magnitude of residues.

Avocado 

A total of 5 field trials were conducted in the United States, EPA Region 10 in order to 

evaluate the magnitude of fluoxastrobin, (E-isomer and Z-isomer)residues in avocado. 

The number and geographic locations of field trials fulfill the US EPA requirements for a 

regional (Region 10) registration on avocado.

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NOF Fluoxastrobin Petition for Tolerance in or on Avocado, Barley, Canola (Rapeseed Subgroup 20A), and Dried Shelled Pea and Bean (Crop Subgroup 6c)

The Evito® 480 SC Fungicide formulation was applied three times using airblast 

application at the maximum proposed label use rate of 0.21 lb ai/A/application. The spray 

volumes ranged from 73 to 75 gallons per acre (GPA) (683 to 711 l/ha) for concentrate 

spray volumes and 150 to 244 GPA (1403 to 2282 l/ha) for dilute spray volumes. Nonionic surfactants (NIS) labeled for agricultural use were added to the spray mixtures. The 

applications were made with a 14-day interval between applications, to support a Region 

10 registration based on a 7-day pre-harvest interval (PHI). Samples were collected from 

both control and treated plots for analysis at normal harvest.

Apparent residues of each analyte were below the LOQ in/on all non-treated control 

samples of avocado RAC samples. No interferences were noted in control samples. 

Residues were not corrected for procedural recovery results. Total residues (E-isomer + 

Z-isomer) ranged from 0.029 to 0.549 ppm (mean = 0.178 ± 0.164, n = 10). 

The maximum storage interval from collection to extraction for analysis was 259 days for 

avocado fruit. Fluoxastrobin (E-isomer and Z-isomer) freezer storage stability has been 

demonstrated in a variety of crop matrices including wheat (forage, grain, and straw), potato 

(tuber), tomato (fruit), and lettuce (head) for 30 months. 

Based on the results of the above residue trials, a tolerance for fluoxastrobin in or on 

Avocado is proposed at 0.9 ppm. 

Barley 

A total of 12 barley trials were established in the U. S. Trials were established in EPA 

Regions 2 (one trial), 5 (three trials), 7 (four trials), 9 (one trial), 10 (one trial), and 11 

(two trials). Trials were conducted on soil types and under cultural practices typical for 

commercial barley production. The number and geographic locations of field trials fulfill 

the requirements for registration on barley as set forth in the Residue Chemistry Test 

Guidelines, OPPTS 860.1500 (Crop Field Trials) and OPPTS 860.1520 (Processed 

Food/Feed) and will fulfill the EPA 40 CFR 158 requirements for registration of 

pesticides.

The treated plots received two foliar broadcast applications of Evito® 480 SC Fungicide 

at 0.125 lb ai/A/application (equal to 0.140 kg ai/ha/application) ±5%. The applications 

were made nominally in 10 gal/A (GPA) ± 10% of spray mix (93.5 L/ha) using foliar 

broadcast ground spray equipment, and a non-ionic surfactant (≥80% ai) at label use rate 

was added to the spray mixtures. Applications were made when the crop was nominally at 

BBCH 37-39 (~80-100% flag leaf emergence) and then 14 ± 1 days after the first 

application. Treated barley hay RAC samples were cut 7 ± 1 days after last application 

(DALA) at all sites

Total residues (E-isomer + Z-isomer) in barley hay, grain, and straw RACs ranged from 

1.10 to 10.1 ppm (mean = 4.97 ± 2.36, n = 24); 0.00749 to 0.281 ppm (mean = 0.0758 ± 

0.0712, n = 24); and 0.133 to 10.1 ppm (mean = 2.05 ± 2.60, n = 24), respectively.

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NOF Fluoxastrobin Petition for Tolerance in or on Avocado, Barley, Canola (Rapeseed Subgroup 20A), and Dried Shelled Pea and Bean (Crop Subgroup 6c)

The barley hay decline data indicate that E+Z-isomer fluoxastrobin residues (corrected 

for % moisture) decrease over the 19-day sampling period with a calculated half-life of 

6.3 days (R2 = 0.9611). The barley grain decline data indicate that E+Z-isomer

fluoxastrobin residues (corrected for % moisture) decrease over the 20-day sampling 

period with a calculated half-life of 12.6 days (R2 = 0.9835). The barley straw decline 

data indicate that E+Z-isomer fluoxastrobin residues (corrected for % moisture) decrease 

over the 20-day sampling period with a calculated half-life of 13.0 days (R2 = 0.9749).

The barley RAC samples were stored frozen (below freezing at the field sites and typically 

at ≤ -10 oC at the analytical laboratory) for a maximum of 196 days from collection to 

extraction for analysis. Barley processed commodities were analyzed within 29 days of 

processing; therefore, freezer storage stability data are not required (OPPTS 860.1380). 

Fluoxastrobin (E-isomer and Z-isomer) freezer storage stability has been demonstrated in a 

variety of crop matrices including wheat (forage, grain, and straw), potato (tuber), tomato 

(fruit), and lettuce (head) for 30 months. 

Based on the results of the above residue trials, a tolerance for fluoxastrobin in or on Barley, 

grain at 0.4 ppm; Barley, hay at 15 ppm; and Barley, straw at 15 ppm.

Canola (Rapeseed Subgroup 20A)

Seventeen canola trials were established in the U. S. and Canada in 2014. Trials were 

established in NAFTA Regions 2 (one trial), 5 (two trials), 7 (two trials), 11 (three trials), 

and 14 (nine trials). Trials were conducted on soil types and under cultural practices 

typical for commercial canola production. The number and geographic locations of field 

trials fulfill the requirements for registration on canola as set forth in the Residue 

Chemistry Test Guidelines, OPPTS 860.1500 (Crop Field Trials), OPPTS 860.1520 

(Processed Food/Feed), PMRA DIR98-02, and PRMA DIR2010-05 requirements for 

registration of pesticides.

The treated plots received two foliar broadcast applications of Evito® 480 SC Fungicide 

at 0.15 lb ai/A/application (equal to 0.168 kg ai/ha/application) (±5%) applied nominally 

28 (27 to 30-day range) and 21 (20 to 22-day range) days before harvest (DBH). The 

applications were made nominally in 10 gal/A (GPA) ± 10% of spray mix (93.5 L/ha) 

using foliar broadcast ground spray equipment, and a non-ionic surfactant (≥80% ai) at 

label use rate was added to the spray mixtures.

Total residues (E-isomer + Z-isomer) in canola seed RAC ranged from 0.0115 to 0.587 

ppm (mean = 0.161 ± 0.138, n = 34). A comparison of the residues in the RAC with 

those in the canola meal and refined oil indicated that the residues do not concentrate 

(processing factors ≤1) in the processed commodities.

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NOF Fluoxastrobin Petition for Tolerance in or on Avocado, Barley, Canola (Rapeseed Subgroup 20A), and Dried Shelled Pea and Bean (Crop Subgroup 6c)

The canola RAC samples were stored frozen (below freezing at the field sites and typically 

at ≤ -10 oC at the analytical laboratory) for a maximum of 145 days from collection to 

extraction for analysis. Fluoxastrobin (E-isomer and Z-isomer) freezer storage stability has 

been demonstrated in a variety of crop matrices including wheat (forage, grain, and straw), 

potato (tuber), tomato (fruit), and lettuce (head) for 30 months. 

Based on the results of the above residue trials, a tolerance for fluoxastrobin in or on Canola

(Rapeseed Subgroup 20A) is proposed at 0.8 ppm. 

Dried Shelled Bean & Dried Shelled Pea (Crop Subgroup 6C)

Eleven dried shelled pea and thirteen (two extra trials were completed) dried shelled bean 

trials were completed in the U. S. and Canada. Trials were conducted on soil types and 

under cultural practices typical for commercial dried shelled pea and dried shelled bean 

production. Dried shelled pea trials were established in NAFTA Regions 7 (three trials), 

11 (five trials), and 14 (three trials). Dried shelled bean trials were established in 

NAFTA Regions 5 (four trials), 7 (two trials), 7a (one trial), 8 (one trial), 9 (one trial), 10 

(one trial), 11 (one trial), and 14 (two trials). The number and geographic locations of 

field trials will fulfill the requirements for registration on dried shelled pea and dried 

shelled bean (Crop Subgroup 6C) as set forth in the Residue Chemistry Test Guidelines, 

OPPTS 860.1500 (Crop Field Trials) and Canadian PMRA Directive 2010-05 and fulfill 

the EPA 40 CFR 158 requirements for registration of pesticides. The treated plots 

received two foliar broadcast applications of Evito® 480 SC Fungicide at 0.15 lb 

ai/A/application (equal to 0.168 kg ai/ha/application) ± 8.7% applied nominally 21 (19 to 

24-day range) and 14 (13 to 18-day range) days before harvest (DBH), except for Trial -

10 which made the applications 14 and 7 DBH. The applications were made in 9.3 to 

13.6 gal/A (GPA) of spray mix (87-127 L/ha) using foliar broadcast ground spray 

equipment, and a non-ionic surfactant (≥80% ai) at label use rate was added to the spray 

mixtures.

Total residues (E-isomer + Z-isomer) in dried shelled bean and dried shelled peas RACs 

ranged from <LOD to 0.146 ppm (mean = 0.0176 ± 0.0300, n = 26) and <LOQ to 0.148 

ppm (mean = 0.0347 ± 0.0366, n = 22), respectively.

The dried shelled bean and dried shelled pea RAC samples were stored frozen (below 

freezing at the field sites and typically at ≤ -10 oC at the analytical laboratory) for a 

maximum of 299 days from collection to extraction for analysis. Fluoxastrobin (Eisomer and Z-isomer) freezer storage stability has been demonstrated in a variety of crop 

matrices including wheat (forage, grain, and straw), potato (tuber), tomato (fruit), and 

lettuce (head) for 30 months, in canola seed for at least 152 days, and in canola meal and 

refined oil for 151 days. These data indicate that fluoxastrobin residues are stable in 

frozen storage for the time periods encountered in this study.

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NOF Fluoxastrobin Petition for Tolerance in or on Avocado, Barley, Canola (Rapeseed Subgroup 20A), and Dried Shelled Pea and Bean (Crop Subgroup 6c)

Based on the results of the above residue trials, a tolerance for fluoxastrobin in or on Dried 

Shelled Pea and Bean (Crop Subgroup 6C) is proposed at 0.2 ppm. 

B. Toxicological Profile 

The complete toxicity profile of fluoxaztrobin was previously published in the Federal 

Register of April 23, 2003 (68 FR19991). 

1. Acute toxicity. Oral and dermal LD50 values were >2000 mg/kg bw. Inhalation LC50

values were >4998 mg/m3 air. Fluoxastrobin technical was not irritating to rabbit skin, was 

moderately irritating to eyes in rabbits and was non-sensitizing dermally in the 

Magnusson/Kligman maximization test in guinea pigs. Acute toxicity studies for 

fluoxastrobin technical support an overall toxicity Category III 

2. Genotoxicty. Several genotoxicity tests were conducted to test for point-mutagenic 

activity, chromosome aberration in vitro and in vivo, and for DNA repair. All tests

conducted were negative, indicating no evidence of mutagenic or genotoxic potential.

3. Reproductive and developmental toxicity. [An oral developmental toxicity study in rat 

did not reveal any evidence of teratogenic potential The maternal NOAELwas300mg/kg 

and the developmental NOAEL was 1000 mg/kg bw/day. An oral developmental toxicity 

study in rabbits demonstrated a maternal NOAEL of 25 mglkg bw/day, a developmental 

NOAEL of 100 mglkg bwlday and did not reveal any teratogenic potential. A twogeneration study in rats, with a parental toxicity NOAEL of 73. 7mg/kgbw/day for males 

and 86.7 mglkgbw/day for females, did not reveal evidence of a primary reproductive 

toxicity potential. The reproductive NOAEL was 763.6 mg/kg bw/day for males and 806.5 

mg/kg bw/day in females.

4. Subchronic toxicity. A subchronic toxicity feeding study with rats over 90 days 

demonstrated a NOAEL of 7.3 and 18.3 mg/kg bw/day for males and females, respectively, 

based on reduced body weights and alterations in several urinary' tract related clinical 

chemistry parameters, at the higher dose levels. In a subchronic feeding study in mice over 

14 weeks a NOAEL was not established based on decreased alanine aminotransferase 

(ALA T) and increased absolute and relative liver weights at the low dose level (21. 7 and 

35.3 mg/kg bw/day for males and females, respectively). A 14-weekfeeding study in dogs 

demonstrated a NOAEL of 3.0 mg/kg bw/day based on decreased body weights and food 

consumption, and liver effects (enzyme induction, increased liver weights and cytoplasmic 

change) and thyroid effects (decreased T3). 

5. Chronic toxicity. A 24-month chronic/oncogenicity feeding study in rats demonstrated a 

NOAEL of 53.0 and 35.2 mg/kg bw/day for males and females, respectively. An 

oncogenicity study in the mouse revealed a NOAEL of 18.5 and 29.5 mg/kg bw/day for 

males and females, respectively based on liver effects. There was no indication in the rat 

or mouse for an oncogenic effect of fluoxastrobin. A one-year feeding study with dogs 

demonstrated a NOAEL of l.7 and 1.5 mg/kg bw/day for males and females, respectively, 

based on decreased body weights and slight liver effects (increased alkaline phosphatase 

(Aph) and liver weights).

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NOF Fluoxastrobin Petition for Tolerance in or on Avocado, Barley, Canola (Rapeseed Subgroup 20A), and Dried Shelled Pea and Bean (Crop Subgroup 6c)

6. Animal metabolism. Metabolism and pharmacokinetic studies in the rats, lactating goats 

and laying hens demonstrate that fluoxastrobin residues are rapidly absorbed, metabolized 

and eliminated. There was no evidence of accumulation of residues in any tissues or organs. 

The metabolic pattern was always complex and numerous metabolites were identified. The 

main metabolic reactions, however, are very comparable for all tested animal species and 

most metabolites were present at low levels. As per the meat and milk tolerances 

established in40 CFR 180.609, the tolerance expression includes fluoxastrobin (sum of E 

and Z isomers) and its phenoxy-hydroxypyrimidine metabolite.]

7. Metabolite toxicology. The residues of concern are fluoxastrobin and its phenoxyhydroxypyrimidine metabolite. This metabolite was investigated for acute oral toxicity and 

point mutagenic activity in a bacterial reverse mutation assay. The phenoxyhydroxypyrimidine metabolite did not show mutagenic activity in the reverse mutation 

assay and the oral LD50 was >300<500 mg/kg body weight.

8. Endocrine disruption. There is no evidence to suggest that fluoxastrobin has any primary 

endocrine disruptive potential. Reproductive and developmental findings provided no 

evidence of an enhanced sensitivity of the young.

C. Aggregate Exposure 

1. Dietary exposure. 

i. Food. A chronic dietary analysis was conducted to estimate exposure to fluoxastrobin 

residues in/on peanuts and peanut oil, refined, at the proposed higher tolerance values in 

addition to tolerances expected or established for all currently proposed and registered crop

uses. Acute analyses were not conducted since, as per EPA's 1/24/05 human health risk 

assessment, there was no indication of an adverse effect attributable to a single dose and 

therefore an acute reference dose (aRfD) was not established. Tier I analysis was conducted 

for the chronic scenario using the DEEM-FCID TM software. Chronic dietary exposure 

estimates from potential residues of fluoxastrobin for the US Population was 30.5% of the 

chronic RfD. The sub-population with the highest exposure was “all infant (<1 year old)” 

with 84.9% of the chronic RfD used. The Tier I assessment utilizes experimentally derived 

and default processing factors, and 100% crop treated information for all registered and 

proposed uses combined. These can be considered very conservative estimates of exposure 

ii. Drinking water. Drinking water was incorporated directly into the DEEM dietary 

assessment under “drinking water” for both “direct” and “indirect” sources using the 

fluoxastrobin the post-breakthrough average concentration modeled for turf which was 

higher than the concentration of 93 ppb that had been previously used in the dietary risk 

assessment. As such, the Tier 1 modeled groundwater concentration of 137 ppb was used 

for drinking water in the chronic dietary risk assessment. 

iii. Aggregate Exposure: No acute aggregate risk assessment was conducted since there 

was no acute endpoint of concern identified.

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NOF Fluoxastrobin Petition for Tolerance in or on Avocado, Barley, Canola (Rapeseed Subgroup 20A), and Dried Shelled Pea and Bean (Crop Subgroup 6c)

Short-term aggregate risks include dietary and non-dietary sources of exposure. The only 

short-term non-dietary exposure comes from the potential for post-application oral 

ingestion (hand-to-mouth activities) by children and inhalation exposure to adults during 

hand-dispersal of granules when treating ornamentals. 

The aggregation involved combining residential exposures with the appropriate chronic 

dietary exposure for children, 1-2 years old (MOE = 113) and the general US population

(MOE = 602). These aggregate MOEs for adults and children are higher than the 

required 100, indicating acceptable short-term aggregate risks.

Long-term aggregate risks are not needed since the residential use pattern for this product 

is not expected to result in residential handler or post-application exposure of more than 6 

months out of the year. 

2 Non-dietary exposure. Post-application risks to the new proposed crops were assessed 

using transfer coefficients from EPA Policy 3 with the maximum proposed application 

rates, eight hours of exposure, and the default assumption of 25% of the application rate 

is available for dislodging. Because there is no short-term dermal point of departure, 

only intermediate-term risks were assessed.

Post-application intermediate-term dermal exposures and risks range from MOEs of

1,600 for hand-harvesting avocados and moving irrigation pipe in dried peas and beans to 

over 50,000 for hand-weeding barley indicating acceptable re-entry risks for agricultural 

workers.

D. Cumulative Effects 

Fluoxastrobin is a novel strobilurin analog. Arysta LifeScienceNorth America, LLC will 

submit information, if necessary, for EPA to consider concerning potential cumulative 

effects of fluoxastrobin consistent with the schedule established by EPA at 62 Federal 

Register 42020 (Aug. 4, 1997) and other EPA publications pursuant to the Food Quality 

Protection Act.

E. Safety Determination 

1. US Population. Using the conservative assumptions described above, based on the 

completeness and reliability of the toxicity data, it is concluded that dietary exposure (food 

and water) from the proposed and registered uses of fluoxastrobin will utilize at most 

30.5% of the reference dose for the US Population, and is likely to be much less as more 

realistic data and models are developed. EPA generally has no concern for exposures below 

100% of the RfD because the RfD represents the level at or below which daily dietary (food 

plus water) exposure over a lifetime will not pose appreciable risks to human health. In 

addition, aggregate (food and water dietary plus residential) MOEs are greater than 100 for 

adults for both short-and intermediate-term exposure durations. Finally, all handler 

exposure scenarios also have MOE greater than 100. Therefore, there is a reasonable 

certainty that no harm will occur to the US Population from aggregate exposure to 

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NOF Fluoxastrobin Petition for Tolerance in or on Avocado, Barley, Canola (Rapeseed Subgroup 20A), and Dried Shelled Pea and Bean (Crop Subgroup 6c)

fluoxastrobin. 

2. Infants and children. Consideration of the toxicology database as described above leads 

to no additional concerns for infants and children. Therefore the FQPA safety factor can 

be established at 1X. All post-application risks for both adults and children exceeded 100, 

indicating acceptable risks. The lowest children’s oral short-term MOE was 180 based on 

hand-to-mouth activities in turf treated with a liquid formulation; this value was used in 

the short-term aggregate risk assessment. 

F. International Tolerances. Codex maximum residue levels (MRLs) are not yet 

established for fluoxastrobin.

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